Peter: Brian, can I see that paper for a sec?
(Brian gives Peter the paper. Peter peruses the paper.)
Peter: Huh… that’s odd… I thought that would big news.
Brian: You thought what would be big news?
Peter: Well there seems to be an absence of a certain ornithological piece: a headline regarding mass awareness of a certain avian variety.
Brian: What are you talking about?
Peter: Oh have you not heard? It was my understanding that everyone had heard…
Brian: Heard what?
Stewie: Brian Don’t!
Peter: OH WELL THE BIRD, BIRD, BIRD, BIRD BIRD IS THE WORD. OH WELL THE BIRD, BIRD, BIRD, BIRD BIRD IS THE WORD. OH WELL THE BIRD, BIRD, BIRD, BIRD BIRD IS THE WORD. OH WELL THE BIRD, BIRD, BIRD, BIRD BIRD IS THE WORD. BRIAN DON’T YOU KNOW ABOUT THE BIRD? WELL PETER IS GOING TO TELL YOU ABOUT THE BIRD. OH WELL THE BIRD, BIRD, BIRD, BIRD BIRD IS THE WORD. OH WELL THE BIRD… SURFINNN BIRD.
Last week the infamous OMFG KILLER FLU WARBLEGARBLE research was finally published. Science put out a special issue almost all about ‘killer bird flu’, editorials, commentary, and the actual research– and ALL of the articles are freely available to everyone!
The research comes in two parts–
1– What does a Bird Flu need to change to turn into a People Flu?
As Ive said before, very simplistically, Bird Flu and People Flu are that way because they like Bird Sugar and People Sugar on Bird and People Proteins. But occasionally Bird Flu can infect people, and it stops there. Bird Flu cant infect people, and then turn into a People Flu. People are a dead-end host for Bird Flu.
But what if it wasnt?
Evolution will find a way…
So, why dont we get one step ahead of evolution? Evolve it in the lab first?
Thats exactly what these folks did. Evolved a Bird Flu that could transmit between mammals, in this case, between the small animal model for influenza, ferrets.
They found that regular ol Bird Flu regularly found the exact same ‘answer’ to the ‘problem’ of mammalian transmission. Five amino acid mutations– four in hemagglutinin (think influenzas Env) and one in basic polymerase 2 (think influenzas Pol). Thats not really all that much, especially for an RNA virus.
Now, just because this happened in the lab doesnt mean it will happen in nature, or, that it will happen this way in nature. But having an answer to how Bird Flu could turn into a pandemic, a virus to study that could turn into a pandemic– it will help us be prepared.
We can study a virus that doesnt even exist yet.
We can study antivirals/develop antivirals for a virus that doesnt even exist yet.
We might have a vaccine to a virus that doesnt even exist yet.
I LOVE THE FUTURE!!!!!
A further benefit is that knowing at least an evolutionary pathway Bird Flu can take means labs working with Bird Flu can keep an eye on their cultures to make sure this guy isnt accidentally evolving under their noses (‘noses’, heh).
2– What are the odds of this actually happening?
In this paper, they data-mined a ton of Bird Flu sequences from all around the world and calculated what needed to happen where for a human transmissible virus to evolve (again, just to stress this point, they looked for one answer that was found in the laboratory– evolution could find another answer in nature).
They considered several factors that could increase the odds:
- “Random mutation” – Viruses mutate. Things happen. Explore sequence space, and youre going to find something.
- “Positive selection” – Things happen. But what if the intermediate steps have a benefit on viral fitness?
- “Long infection” – Virus can get comfy in its new environment.
- “Functionally equivalent substitutions” – Some amino acids kinda look/act alike. Wink is the same as a blink to a blind man.
- “Avian-to-mammal transmission of partially adapted mutants” – We are assuming bird-to-human. What if the bird flu already has three of the necessary mutations on its own, just by chance?
- “Mammal-to-mammal transmission of partially adapted viruses” – These five mutations might be the ‘best’ (well, good enough, evolutionarily), but what if two mutations can be transmitted between mammals, but less optimally?
And several factors that could decrease the odds:
- “An effective immune response” – If we can readily neutralize these guys (cross-reactivity of antibodies) then it dont much matter, does it?
- “Deleterious intermediate substitutions” – Edge of evolution! LOL! No, for real, sometimes you cant get from A to , evolutionarily.
- “Order dependence in the acquisition of substitutions” – Making 5 mutations is one thing. Making 5 mutations in a precise order is something else.
Of course the risks were different for every simulation they ran. So they came to a few conclusions on how we can better protect ourselves (this paper was a series of lists. I didnt necessarily mind that, but it actually make me lol):
- “Additional surveillance in higher-risk regions” – We know what to look for. From previous sequence data, we know which regions are more likely to produce mammal transmissible Bird Flu.
- “Deep sequencing of avian and other nonhuman virus samples” – The more sequences we have, the more accurate our predictions will be.
- “Which substitutions, besides the already identified receptor-binding substitutions […] are capable of producing respiratory droplet–transmissible A/H5N1 viruses” – Again, we have an answer to mammal-to-mammal transmission. How many different ways are there to fly? How many different ways are there to see? How many different ways can this virus evolve to be mammal transmissible?
- “Within-host fitness and between-host transmissibility” – We need to study this virus more in the lab.
So thats it. Thats what the big hubub was about. Really cool research with really cool implications. I have no friggen clue why the US government freaked out. And Im not saying that sarcastically.